Elsevier

The Annals of Thoracic Surgery

Volume 68, Issue 3, September 1999, Pages 1034-1038
The Annals of Thoracic Surgery

Original Articles: General Thoracic
Tumor angiogenesis and recurrence in stage I non-small cell lung cancer

https://doi.org/10.1016/S0003-4975(99)00611-6Get rights and content

Abstract

Background. Tumor angiogenesis appears to relate to recurrence after an operation as a route for distant metastasis. We assessed the association of vascular endothelial growth factor (VEGF) expression and intratumoral microvessel density (MD) with recurrence in primary lung cancer.

Methods. Samples were randomly obtained from 104 stage I lung cancer patients who underwent curative operations (43 recurrent, 61 nonrecurrent patients). Microvessels were highlighted by staining endothelial cells for factor VIII and VEGF antigen was detected using a polyclonal antibody.

Results. VEGF antigen was detected in large amounts in both recurrent (100%) and nonrecurrent tumors (73.8%). The percentages of patients with the strongest VEGF stain (more than 50% of staining area in tumor cells) were 46.5% in tumors with recurrence and 11.5% in tumors without recurrence. The mean MD in recurrent and nonrecurrent tumors were 18.2 ± 10.5 and 8.5 ± 5.0, respectively, resulting in a significantly greater value in tumors with recurrence (p < 0.0001). Although there were no significant differences in mean MD according to pathological types, in adenocarcinoma and adenosquamous carcinoma, the mean value in the recurrent group was significantly greater than that in the nonrecurrent one.

Conclusions. An evaluation of VEGF expression and MD in tumors may contribute to the estimation of the risk of recurrence of non-small cell lung cancer in early stages.

Section snippets

Patients and methods

Tumor samples were randomly obtained from 104 primary lung cancer patients in stage I who received curative operations with routine systematic nodal dissection of both the hilar and the mediastinal lymph nodes as previously described 7, 8 in Kanazawa University Hospital from 1988 to 1993. In follow-up periods longer than 5 years, 43 patients died from recurrent lung cancer and 61 patients survived without any recurrence. In the recurrent group (n = 43), the 34 men and 9 women had a mean age of

Results

The 3- and 5-year survival rates for the patients in the recurrent group (n = 43) were 34.9% and 14.0%, respectively, having a significantly worse prognosis as compared to those (both 100%) in the nonrecurrent group (p < 0.01).

The percentage of VEGF positive tumors and that of tumors with the strongest VEGF stain (more than 50% of the staining area in tumor cells) were 88.9% (48 of 54) and 29.6% (16 of 54) in adenocarcinomas, 80.6% (25 of 31) and 16.1% (5 of 31) in squamous cell carcinomas, and

Comment

In non-small cell lung cancer, Macchiarini and associates [1] first observed a relationship between neovascularization and metastasis in 1992. In 1994, Yamazaki and associates [2] found that angiogenesis, which was assessed by counting microvessels in lung adenocarcinomas, was positively correlated with the relapse of patients after an operation, and they also suggested that microvessel counts in tumors were associated with the aggressiveness of the tumor. Since then, multi-institutional

References (17)

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